The etiology of SLE is incompletely understood; it has a genetic basis, although environmental and/or stochastic factors likely contribute to disease pathogenesis. Epidemiological studies suggest EBV plays a role in the etiopathogenesis of SLE. Patients with SLE have a forty-fold increased mean EI3V viral load compared to healthy controls, a finding recently confirmed. The increased presence of EBV in lupus may contribute to disease genesis, and might be a consequence of increased viral susceptibility and/or abnormalities in immune control of viral infection secondary to aberrant immune responses inherent in patients with systemic autoimmunity. Although EBV has not been proven to initiate disease in SLE, it could contribute to autoimmune phenomena via induction of type I interferons. Herpes viruses have been shown to induce IFN-alpha production from plasmacytoid dendritic cells (pDC) through a TLR-9 mechanism. Numerous studies suggest type I interferon's induce autoimmunity and, in particular, SLE. The use of IFN-alpha for the treatment of hepatitis C and leukemia can cause SLE-like illness, and IFN-alpha levels are elevated in lupus patients. Micro array studies using DNA from peripheral blood cells of lupus patients demonstrate increased IFNalpha- induced gene expression. These patients have greater SLEDAIs (SLE Disease Activity Index) and a history of more severe disease. Based on these studies, the hypothesis is raised that: he inability to completely control Epstein Barr virus (EBV) infection in patients with systemic lupus erythematosus (SLE) results in IFN-alpha production that contributes to disease pathogenesis. To address this hypothesis, the following aims will be undertaken: 1) Determine why EBV viral loads are increased in patients with SLE, 2) Determine if exogenous EBV can induce type IIFN production by plasmacytoid dendritic cells (pDC), 3) Correlate EBV viral loads with evidence of type I IFN up-regulation and disease activity in patients with SLE, 4) Determine if increased spontaneous outgrowth of EBV-infected B cells induce IFN-alpha production by pDC from lupus patients.